Safety and effectiveness of budesonide rectal foam for ulcerative colitis in a large-scale, multicenter, prospective observational study: final report of post-marketing surveillance in Japan

Masayuki Saruta; Teppei Omori; Akira Nagaki; Yuki Arai; Minami Umeyama; Shinsuke Kurosu; Kiyotoshi Kuramoto; Yasuo Suzuki

doi:10.5217/ir.2025.00164

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Original Article Safety and effectiveness of budesonide rectal foam for ulcerative colitis in a large-scale, multicenter, prospective observational study: final report of post-marketing surveillance in Japan: Masayuki Saruta¹, Teppei Omori², Akira Nagaki³, Yuki Arai³, Minami Umeyama³, Shinsuke Kurosu³, Kiyotoshi Kuramoto⁴, Yasuo Suzuki⁵; DOI: https://doi.org/10.5217/ir.2025.00164
Published online: February 11, 2026

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

²Department of Gastroenterology and Hepatology, Kyorin University Suginami Hospital, Kyorin University School of Medicine, Tokyo, Japan

³EA Pharma Co., Ltd., Tokyo, Japan

⁴Kissei Pharmaceutical Co., Ltd., Tokyo, Japan

⁵Ginza Central Clinic, Tokyo, Japan

Correspondence to Masayuki Saruta, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. E-mail: m.saruta@jikei.ac.jp

• Received: July 31, 2025 • Revised: October 24, 2025 • Accepted: November 13, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
Graphical abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
NOTES
Supplementary Material
REFERENCES

Abstract

Background/Aims
Budesonide rectal foam was approved in Japan in 2017 for mild to moderate active ulcerative colitis (UC). This is the final report of post-marketing surveillance to evaluate real-world safety and effectiveness.
Methods
This Japanese large-scale, prospective, multicenter, open-label observational study included patients with active-phase mild to moderate UC newly started on budesonide 2 mg rectal foam. Safety was evaluated by adverse drug reactions (ADRs). Effectiveness was evaluated using clinical remission rates and partial Mayo scores. Effectiveness by background (disease phenotype, severity, clinical course, age, prior topical therapy, baseline advanced therapy [biologicals/Janus kinase inhibitors]) was also assessed.
Results
There were 633 and 503 patients in the safety and effectiveness analyses, respectively. ADRs occurred in 4.3% (27/633) of patients. Eight glucocorticoid-related ADRs occurred in 7 patients (1.1%). Clinical remission rates were 44.2% (165/373), 72.1% (191/265), and 69.8% (333/477) at week 2, week 6, and the final evaluation, respectively. There were statistically significant changes from baseline in partial Mayo scores at all timepoints (all P< 0.0001 vs. baseline). At 2, 4, 6, and 6–12 weeks, mean± standard deviation changes from baseline in partial Mayo scores were −2.1 ± 1.9, −2.7 ± 2.1, −3.1 ± 2.3, and −3.4 ± 2.3 points, respectively. Statistically significant improvements were maintained at all timepoints in subgroup analyses by background (disease phenotype, severity, clinical course, age, prior topical therapy, baseline advanced therapy).
Conclusions
No new safety concerns were identified. Partial Mayo score improved in a variety of patient background factors. Health condition improvements were confirmed in this Japanese post-marketing surveillance. (Japan Registry of Clinical Trials, identifier jRCT1080223802)
Keywords: Budesonide; Surveillance; Therapeutics; Ulcerative colitis

Graphical abstract

INTRODUCTION

Ulcerative colitis (UC) is a diffuse, idiopathic chronic inflammation of the colon that often results in friability and erosions, leading to bleeding [1]. It typically starts in the rectum, extends proximally into the colon, and is characterized by repeated flare-ups and remissions. In the 2020 Japanese evidence-based clinical practice guidelines for inflammatory bowel disease, oral or topical 5-aminosalicylic acid (5-ASA) is the first-line treatment for mild to moderate UC [2]. However, not all patients achieve adequate disease control with 5-ASA treatment. A clinical study evaluating the optimum dose of oral 5-ASA in maintaining remission in patients with UC found that less than one-third of patients remained in remission after 12 months [3]. In patients with active UC in whom response to 5-ASA is inadequate, additional treatment, including corticosteroids, may be required.

Budesonide is a synthetic glucocorticoid with high topical anti-inflammatory activity and high first-pass metabolism, resulting in low systemic exposure [4]. Budesonide 2-mg rectal foam is a formulation that delivers a foam containing 2 mg of budesonide from the rectum to the sigmoid colon in a single push. The properties of this formulation result in high retention of the drug in the intestinal tract, with negligible leakage of the drug through the anus after administration.

Two identically designed, international phase 3 randomized, placebo-controlled clinical trials of budesonide 2-mg rectal foam evaluated its efficacy in inducing remission in 546 patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis [5]. At week 6, remission was statistically significantly more frequent among patients receiving budesonide foam versus placebo (study 1, 38.3% vs. 25.8%, P=0.0324; study 2, 44.0% vs. 22.4%, P<0.0001); similarly, more patients receiving budesonide foam achieved resolution of rectal bleeding [5]. In Japan, a multicenter, phase 3 placebo-controlled trial in 126 patients with mild to moderate UC and active inflammation in the distal colon also found that both complete mucosal healing of distal lesions and clinical remission were improved with budesonide versus placebo [6].

Budesonide foam was approved for manufacturing and marketing in Japan in September 2017 for treating mild to moderate UC. Post-marketing surveillance was initiated in 2018 to evaluate the safety, effectiveness, and acceptance of the drug in patients with UC in real-world clinical use, with interim results published in 2021 [7]. In the interim analysis, data collected from February 1, 2018 to April 26, 2019 from 182 patients who received budesonide 2-mg rectal foam were evaluated, with the results suggesting that the treatment had a good safety profile in clinical practice. At week 6, clinical remission rates were approximately 68%, and around 3 quarters of patients reported good compliance. Overall, treatment was considered acceptable to patients, eliciting improvements in clinical symptoms.

The final Japanese post-marketing surveillance of the safety and effectiveness of budesonide 2-mg rectal foam in realworld clinical practice is presented here.

METHODS

1. IRB/IACUC Approval

The study was performed per the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. It was conducted in compliance with the guidelines of the Good Post-marketing Study Practice for drugs according to the Ministry of Health, Labour and Welfare ministerial ordinance in Japan. Although the Japanese Pharmaceuticals and Medical Devices Agency and the Japanese Ministerial Ordinance on Standards for Post-marketing Surveys do not require patient informed consent or approval of the research protocol by the ethics review committee at each medical institution, the research protocol was reviewed and approved by the regulatory authority before the study began, and verbal informed consent was obtained from all patients before registration. This study was registered in the Japan Registry of Clinical Trials under the identifier jRCT1080223802.

2. Description of Participants

Patients with active-phase mild to moderate UC who had been newly started on budesonide rectal foam were included. Patients with severe UC were excluded from the study. The severity of UC was based on the judgment of the treating physician.

3. Intervention

All patients who received budesonide 2-mg rectal foam were included in the safety analysis population. Patients adhering to the approved dosage regimen and administration (1 push of budesonide foam 2 mg twice daily for adults, administered rectally) were included in the effectiveness analysis population. Cases involving off-label use, defined as use in pediatric patients or non-approved dosing schedules such as once-daily administration, were excluded from the effectiveness analysis because of the potential for confounding pharmacokinetic and clinical responses.

The standard duration of administration was 6 weeks, with the patient’s condition to be closely monitored during treatment. The duration of administration could be shortened or extended depending on its efficacy. However, in line with the Japanese prescribing information [8], administration beyond 6 weeks was to be considered carefully, with the drug not administered indiscriminately. The treating physician made the final decision on dosage, frequency, and duration of administration.

4. Safety Outcomes

Data were collected on adverse events (AEs), including date of onset, severity, whether the drug was discontinued, causal relationship with the drug, treatment, outcome, date of outcome determination, and laboratory values related to the AE. AEs for which a causal relationship with the study drug could not be ruled out were defined as adverse drug reactions (ADRs). Safety was also evaluated based on patient background factors. ADRs were classified by system organ class and preferred term using the Medical Dictionary for Regulatory Activities Japanese version 24.0.

5. Effectiveness Outcomes

Effectiveness was assessed by evaluating clinical remission rates in partial Mayo score and change in partial Mayo score and its subscores (stool frequency, rectal bleeding, and physician’s global assessment) [9].

Other assessments included details of treatment with budesonide rectal foam, time to remission, evaluation of health condition using the visual analogue scale (VAS), and subgroup analyses of partial Mayo score by background factors (disease phenotype, severity, clinical course, age, prior administration of topical therapy, and biological agent or Janus kinase inhibitor use at baseline, referred to herein as advanced therapy). Any difference in effectiveness by age ( <65 and ≥65 years) was also assessed. Patient acceptance, convenience, and the time to feel the treatment effects were investigated using a self-administered paper questionnaire (Supplementary Methods), with the physician noting the results on the case report forms.

Logistic regression analyses were conducted to determine factors affecting clinical remission.

Colonoscopy or sigmoidoscopy was used as part of routine clinical practice to identify the most active disease areas in the rectum and sigmoid colon and score the endoscopic findings. Findings were evaluated at baseline, during, and at the end of treatment using the Mayo endoscopic subscore [9].

6. Sample Size

The number of cases to be evaluated for safety considerations was set at 600 to ensure a 95% probability that at least 1 unknown ADR occurring at a frequency of ≥0.5% would be detected in at least 1 case based on the results of domestic phase 2 and phase 3 clinical trials [6,10].

7. Statistical Analysis

Summary statistics were calculated for patient background characteristics and dosages at each evaluation timepoint. For the safety analysis, the incidence rate of ADRs was calculated.

Partial Mayo scores were collected at the start of administration (Day −1 to 0), at 2 weeks (Days 1–20), at 4 weeks (Days 21–34), at 6 weeks (Days 35–48), at 6–12 weeks (Days 49–84), and beyond 12 weeks (Day 85 onwards). Data were treated as missing for any assessment timepoint if drug administration had already ended or if the patient lacked an assessment within the designated window. The last available assessment data point collected after the start of administration for each patient was designated as the final assessment. Clinical remission rates based on the partial Mayo score [9] were calculated with 95% confidence intervals (CIs) at each timepoint. Clinical remission was defined as a partial Mayo score of ≤ 2 points and all subscores of ≤ 1 point. The Kaplan–Meier method was used to estimate the cumulative time to clinical remission (days). The calculation of time to clinical remission in days was determined using the visit date on which the patient met the criteria during a scheduled clinical assessment. Summary statistics were calculated for partial Mayo score [9] and subscores at each evaluation timepoint. For changes in partial Mayo score and each subscore, a Wilcoxon signed-rank sum test (one-sample Wilcoxon test) was used to compare the change from baseline and mean ±standard deviation (SD) time-course changes were plotted. Subgroup analyses for partial Mayo scores performed for disease phenotype, severity, clinical course, age, prior use of topical therapy, and baseline use of advanced therapy were plotted by mean±SD time-course changes. Additionally, a two-sample t-test was performed on the mean change in partial Mayo score at each timepoint by age group (<65 and ≥ 65 years).

For evaluating health conditions using the VAS (whereby a score by the patient of 100 indicated the best imaginable state and a score of 0 indicated the worst imaginable state), summary statistics were calculated for each timepoint. A one-sample t-test was performed by calculating the 95% CI for the mean change. Mean ±SD time-course changes were plotted. The scores obtained for each question of the patient questionnaire were tabulated by frequency for each evaluation timepoint. For the time it takes to notice the effects of treatment, patients could choose from the following on the self-administered questionnaires: 1–3 days, 4 days to 1 week, 1–2 weeks, 2–4 weeks, 4–6 weeks, or 6 weeks onwards until present to feel the effects; or that they did not feel any effects.

Univariate logistic regression analysis was performed with clinical remission (none/present) in partial Mayo score at the final evaluation as the objective variable and patient background factors as the explanatory variables. Multivariate logistic regression analysis was performed with the patient background factors that were significant in the univariate analysis as explanatory variables, and the number of cases of remission, remission rate (%), odds ratio (OR), 95% CI, and P-values were calculated. The stepwise method was used for variable selection, and the criteria for inclusion and exclusion in the model were set at 5%.

For each evaluation period, summary statistics were calculated for endoscopy scores. Summary statistics were calculated for the change from baseline to the end of treatment, and a one-sample Wilcoxon test was performed.

Analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA).

RESULTS

1. Patient Disposition

From the start to the end of the study, 655 patients were enrolled at 204 facilities, and 645 case report forms were obtained. After excluding 12 patients (5 for no treatment with the drug and 7 for no further visits), 633 patients were included in the safety analysis population. After excluding 130 patients with off-label use, 503 patients were included in the effectiveness analysis population (Fig. 1).

2. Patient Demographics and Baseline Characteristics

Table 1 shows the demographic characteristics of the 633 patients in the safety analysis population. Just over half (53.7%, 340/633) were male; the mean±SD age was 45.6 ±15.6 years. Approximately one-third (29.9%, 189/633) had a duration of disease ≥1 and <5 years; 38.7% (245/633) had pancolitis, 39.5% (250/633) had left-sided colitis, and 21.8% (138/633) had proctitis. Overall, 67.3% (426/633) had disease of moderate severity and 68.4% (433/633) had relapsing–remitting UC. Almost all (96.7%, 612/633) received concomitant medications for UC; 91.5% (579/633) received oral 5-ASA preparations (Table 1). Of the 579 patients who received concomitant 5-ASA preparations, 42.4% received a dose >4,000 mg/day. The mean±SD 5-ASA dosage was 3,904.4 ±948.1 mg/day (Supplementary Table 1).

3. Treatment Duration

Table 2 shows details of treatment with budesonide 2-mg rectal foam during the study. The median (interquartile range) treatment duration was 56.0 days (38.0–85.0 days). When grouped by treatment duration (n =633), 29 patients (4.6%) were treated for <2 weeks. Most patients received treatment for ≥6 weeks, with 143 (22.6%) for ≥2 weeks to <6 weeks, 281 (44.4%) for ≥6 weeks to ≤12 weeks, and 180 (28.4%) for >12 weeks. Among the patients who ended treatment by 12 weeks (n =453), the primary reason for discontinuation was improvement of disease condition (69.5%). Less frequent reasons included lack of effectiveness (15.2%), failure to attend follow-up visits and treatment refusal (each 4.2%), AEs (2.4%), and other reasons (5.3%). Over 3 quarters of patients (79.6%, 504/633) used twice-daily dosing of budesonide 2-mg rectal foam, which is the approved dosage regimen in Japan.

4. Safety

The incidence rates of ADRs are shown in Table 3. ADRs occurred in 4.3% of patients (27/633), with all cases resolving or recovering. The occurrence by administration period was as follows: 11 cases (10 non-serious, 1 serious) among those treated for <6 weeks; 12 cases (11 non-serious, 1 serious) among those treated for 6–12 weeks; and 4 cases (all non-serious) among those treated for >12 weeks. The most common ADR was headache (occurring in 4 patients [0.6%]). Eight glucocorticoid-related ADRs occurred in 7 patients (1.1%), which were cystitis, gastroenteritis, gastroenteritis viral, nasopharyngitis, insomnia, hypertension, acne, and edema. Serious ADRs were 1 case (0.2%) of cytomegalovirus enterocolitis in a patient treated for <6 weeks and 1 case (0.2%) of infectious enteritis in 1 patient treated for 6–12 weeks; both cases resolved. No deaths or ADRs leading to death occurred during the study. Safety was also evaluated based on the patient’s background (Supplementary Table 2). During the study, 3 patients were aged <15 years, and 4 had renal dysfunction; no ADRs occurred in these patients. The incidence of ADRs in patients aged ≥65 years was 3.4% (3/88; 95% CI, 1.2%–9.5%) and in patients with hepatic dysfunction was 10.0% (1/10; 95% CI, 1.8%–40.4%).

5. Effectiveness

Fig. 2 shows effectiveness by partial Mayo score and subscores. Clinical remission rates in partial Mayo scores increased throughout the study, reaching 44.2% (95% CI, 39.3%–49.3%; 165/373) at 2 weeks, 72.1% (95% CI, 66.4%–77.1%; 191/265) at 6 weeks, and 69.8% (95% CI, 65.5%–73.8%; 333/477) at the final evaluation (Fig. 2A). The median time to clinical remission (days) estimated using the Kaplan-Meier method was 29.0 (95% CI, 28.0–29.0) (Supplementary Fig. 1).

There were statistically significant changes from baseline in partial Mayo score at all timepoints (all P<0.0001 vs. baseline) (Fig. 2B). At 2, 4, 6, and 6–12 weeks, mean±SD changes from baseline in partial Mayo score were −2.1 ± 1.9, −2.7 ± 2.1, −3.1 ± 2.3, and −3.4±2.3 points, respectively. Statistically significant changes in each subscore of the partial Mayo score (stool frequency, rectal bleeding, and physician’s global assessment) were also observed (all P<0.0001 vs. baseline) (Fig. 2C-E). The proportion of patients with a rectal bleeding score of 0 increased throughout the study (48.8%, 72.1%, and 70.2% at 2 weeks, 6 weeks, and at the final evaluation, respectively) (Supplementary Fig. 2).

Fig. 3 shows the breakdown of the partial Mayo score by background factors (disease phenotype, severity, clinical course, and age), with statistically significant improvements maintained at all timepoints (Fig. 3A-D). The statistically significant improvements in partial Mayo score were also maintained in the breakdown by prior use of topical therapy (Fig. 3E) and by using advanced therapy at baseline (Fig. 3F). Of note, in the comparison of effectiveness by age group (<65 and ≥65 years), there were no statistically significant differences between the 2 groups at any evaluation timepoint (all P>0.05) (Fig. 3D).

There was a statistically significant improvement in health condition VAS compared with the start of treatment at all evaluation timepoints (P<0.0001) (Supplementary Fig. 3). Most patients who responded (85.8%; 307/358) felt effects within the first 2 weeks of treatment (Supplementary Fig. 4). Overall, 71.2% (358/503) of patients felt effects; 10.5% (53/503) did not.

Table 4 shows factors affecting clinical remission. In multivariate analyses, factors associated with remission included a partial Mayo score of 0–3 at treatment initiation (OR, 2.749; 95% CI, 1.165–6.486; P=0.0210), relapsing–remitting clinical course (OR, 0.334; 95% CI, 0.165–0.677; P=0.0023), prior administration of topical therapy (OR, 0.433; 95% CI, 0.257–0.728; P=0.0016), and prior administration of advanced therapy (OR, 0.298; 95% CI, 0.135–0.657; P=0.0027). Patients with a partial Mayo score 0–3 at the start of treatment were more likely to achieve remission compared with those with a score of 3–6. Patients with a relapsing–remitting clinical course had a lower likelihood of achieving remission compared with those with first-onset disease. Similarly, patients who received topical therapy or advanced therapy prior to this drug had a lower likelihood of achieving remission compared with those who did not receive such therapies.

There were statistically significant reductions in endoscopy scores at the end of treatment versus baseline (P<0.0001) (Supplementary Fig. 5).

6. Patient Acceptance

The results of the self-administered questionnaire on patient acceptance are shown in Supplementary Table 3. The response rates (number of responding patients/number of patients included in the analysis) for the questionnaire item ‘adherence’ at each evaluation timepoint were 76.3% (384/503) at 2 weeks, 73.0% (316/433) at 4 weeks, 70.9% (265/374) at 6 weeks, and 68.7% (171/249) at 6–12 weeks. Response rates for other survey items were similar. At 2 weeks, good or mostly good adherence was reported by 89.3% of patients (343/384). This was sustained throughout the study, with 88.0% (382/434) of patients reporting good or mostly good adherence at the final evaluation. In terms of convenience, at 2 weeks, the majority of patients reported that budesonide rectal foam was very easy or rather easy to use (83.3%; 319/383); at the final evaluation, 89.6% (388/433) of patients reported that the product was very easy or rather easy to use. Regarding leakage of the foam from the anus, the majority of patients throughout the study (83.3%–91.8%) reported that there was none or almost none at all.

DISCUSSION

This Japanese post-marketing surveillance study evaluated real-world safety, effectiveness, and patient acceptance in patients with mild to moderate UC who had newly started on budesonide rectal foam. Budesonide is a synthetic glucocorticoid with high first-pass metabolism and low bioavailability [4]. This results in low systemic exposure, with systemic ADRs considered rare. In the current study, the incidence of ADRs was 4.3%, which is not substantially higher than that reported in the interim results of the study (3.8%) [7]. Except for 2 ADRs (cytomegalovirus enterocolitis and enteritis infectious in 1 patient each; both patients recovered), all were non-serious.

The incidence of glucocorticoid-related ADRs was 1.1% in this final analysis. All glucocorticoid-related ADRs were nonserious, suggesting a minimal effect on cortisol levels. However, it must be noted that the impact on cortisol levels was only assessed in terms of ADRs, as plasma cortisol levels were not routinely measured. In 2 international placebo-controlled clinical trials of budesonide foam [5], efficacy (clinical remission rate and bleeding score at 6 weeks) was superior to placebo. Transient decreases in mean cortisol concentrations were observed during twice-daily dosing with budesonide foam, but levels returned to baseline by week 6. The results of this postmarketing surveillance showed that the drug was administered for ≥6 weeks in over 70% of patients. Although no tendency was observed for an increased incidence of serious ADRs in patients treated for more than 6 weeks, as noted in the Japanese prescribing information, to optimize the drug’s safe use, it is necessary to closely observe the patient’s condition when it is administered beyond a 6-week time period [8]. In this post-marketing surveillance, no patient background factors that could affect the occurrence of ADRs were identified, supporting the drug’s safety profile.

In the current study, approximately 80% of patients used budesonide foam twice daily. In a pooled analysis of phase 2 and 3 trials of budesonide foam, twice-daily administration increased the probability of early response and a better prognosis after stopping treatment following endoscopic remission [11]. The current study found similar effectiveness (assessed by partial Mayo score).

In terms of effectiveness, statistically significant changes from baseline in partial Mayo score were observed at 2, 4, 6, and 6–12 weeks (all P<0.0001 vs. baseline), indicating effectiveness shortly after the start of administration. Statistically significant changes in each subscore of the partial Mayo score (stool frequency, rectal bleeding, and physician’s global assessment) were also observed (all P<0.0001 vs. baseline). The clinical remission rate in partial Mayo score was almost 70% at the final evaluation. Notably, at 2 weeks the rate was approximately 44%, and almost 50% of patients reported no bloody stools after 2 weeks, reinforcing the almost immediate effect of the treatment. The self-administered questionnaire also supported the early effects of budesonide rectal foam, in which approximately 86% of patients reported that they felt effects within 2 weeks of the start of this treatment.

An important aspect of this post-marketing surveillance is stratification of patients not only by disease phenotype, which was reported in the interim analysis [7], but also by severity, clinical course, age, prior administration of topical therapy, and use of advanced therapy at baseline. Statistically significant improvements in partial Mayo score were observed at all timepoints in all these subgroups. In terms of disease severity, the study confirmed that partial Mayo score improved to the same level at 6–12 weeks in both patients with UC of moderate severity and in those with mild disease. Regarding clinical course, similar improvements in scores were observed not only in patients with first-onset disease, but also in those with relapsing– remitting or chronic continuous course.

As people age, ease of use of treatment formulations becomes increasingly important. Furthermore, additional attention regarding the risk of infection and the use of treatments such as immunosuppressants may be required [12]. Similar improvements in partial Mayo score were observed in the analysis by age group (<65 and ≥ 65 years) in this study, suggesting that budesonide foam might be an appropriate option as a remission-inducing treatment in older patients as well.

The present study also explored factors affecting clinical remission. Induction of remission was more likely to be achieved in patients with a lower partial Mayo score at the start of treatment compared with those with higher scores, indicating that the use of budesonide foam at an earlier, milder stage of symptoms may be associated with more favorable clinical outcomes. Patients with a relapsing–remitting clinical course or those who used topical or advanced therapy (suggesting more advanced disease), had a lower likelihood of remission compared with patients with first-onset disease or those who had not previously used such treatments. Nevertheless, statistically significant improvements were observed from 2 weeks in these groups, with remission rates at the final evaluation of 59.0%, 48.8%, and 35.5%, respectively. This indicates budesonide foam might still be an option for the induction of remission in patients with more established disease or those already receiving treatment.

Achievement of complete mucosal healing of distal UC with 2-mg budesonide foam treatment has been reported in Japanese phase 2 and 3 studies [6,10]. The current study adds to the findings of these trials by including a larger number of patients and evaluating real-world use. The effectiveness and safety profiles were similar, and no new safety concerns were identified.

Regarding induction therapy for proctitis, Japanese clinical practice guidelines recommend that, if the condition does not improve with treatment using oral or suppository/enema 5-ASA preparations, budesonide rectal foam should be added to 5-ASA treatment. Similarly, regarding induction therapy for mild to moderate left-sided colitis and pancolitis, if the inflammation of the left-sided colon is severe, budesonide rectal foam in combination with oral 5-ASA preparations may be considered [2]. The patterns of oral 5-ASA use in this post-marketing surveillance, whereby approximately 90% of patients had previously received or were concomitantly treated with oral 5-ASA, align with these recommendations.

A multicenter phase 3 study compared budesonide rectal foam with placebo enema or budesonide enema with placebo foam in patients with active ulcerative proctitis or proctosigmoiditis [13]. The effectiveness and safety of the budesonide enema and foam formulations were similar. However, because of better tolerability and application, the study authors reported that most patients (84%) preferred the foam formulation [13], which is aligned with the high patient acceptability of the foam formulation in the current study and previous reports [14]. The present study also confirmed a statistically significant improvement in health condition evaluated using the VAS from week 2 after the start of administration of budesonide foam, suggesting improved quality of life. A Japanese study of budesonide rectal foam in patients with UC reported significant improvements in both nocturnal diarrhea and urgent defecation, which are among the factors that may contribute to poor quality of life in patients with this condition [15].

In the self-administered questionnaire in this post-marketing surveillance, patients reported good or mostly good adherence and that the drug was easy or rather easy to use. The questionnaire also collected information on other aspects of acceptability to patients, including posture during application, container operability and leakage of foam from the anus, all of which elicited broadly positive responses. These findings regarding adherence and convenience of the budesonide foam formulation are supported by the results of a Japanese survey of topical therapies for UC, in which the rate of satisfaction was higher for a foam formulation than enemas or suppository formulations [16]. Taken together, the good acceptability of the budesonide foam formulation in the current post-marketing surveillance may have contributed to the good adherence and, thus, the clinical effectiveness observed. Budesonide is also available as an oral multi-matrix (MMX) formulation, which is widely available internationally and has been approved in Japan [17]. European and U.S. treatment guidelines recommend the MMX formulation for remission induction in adult patients with mild to moderate active UC who are intolerant or non-responsive to 5-ASA [18,19]. Because the administration routes of foam and MMX budesonide preparations vary, differences in usage and among target patients need to be considered in the future.

This study has some potential limitations. Because of its design as a post-marketing surveillance study, no strict criteria were defined for patient background at the time of initiation of treatment or for previously used or concomitant medications, although this does reflect real-life use. Because of the lack of placebo or comparator controls, the existence of bias could not be ruled out. Furthermore, because this study only observed patients for up to 12 weeks, the safety of administration beyond this time period cannot be assessed. Additionally, the self-administered patient acceptance questionnaire had not been validated. Mucosal healing could not be fully evaluated because few patients had endoscopic data before and after treatment. Given the observational nature of this study, the endoscopic examinations were performed as needed as part of clinical practice to assess the extent of lesions and the degree of inflammation. As such, the findings regarding endoscopy scores are for reference purposes only. Similarly, as plasma cortisol levels were not routinely measured, findings on glucocorticoid-related effects should be interpreted with caution. Finally, the study was conducted in Japanese patients and may not be generalizable to other settings.

In summary, this post-marketing surveillance represents a large-scale prospective observational study conducted at multiple facilities, and, to the best of our knowledge, it is the largest clinical study to date evaluating budesonide rectal foam. No new safety concerns were identified for the budesonide rectal foam formulation in Japanese patients with mild to moderate UC. Effectiveness, acceptability to patients, and improvements in health conditions were confirmed in the setting evaluated in this study. Effectiveness was maintained in a variety of patient background factors—disease phenotype, severity, clinical course, age, and the use of topical or advanced therapy—that might be encountered in real-world clinical practice.

NOTES

Funding Source

This study was funded by EA Pharma Co., Ltd. and Kissei Pharmaceutical Co., Ltd., Japan.

Conflict of Interest

Saruta M has received research grants or contracts from AbbVie G.K., CMIC CMO Co., Ltd., Zeria Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., and Janssen Pharmaceutical K.K.; and payments or honoraria from AbbVie G.K., EA Pharma Co., Ltd., Gilead Sciences K.K., Janssen Pharmaceutical K.K., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nobelpharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Viatris Pharmaceutical Co., Ltd. Omori T has received gratuities from Takeda Pharmaceutical Company Limited, and AbbVie G.K. Suzuki Y has received gratuities from Takeda Pharmaceutical Company Limited, AbbVie G.K., Mochida Pharmaceuticals, Mitsubishi Tanabe Pharma Corporation, and Janssen Pharma, Inc. Nagaki A, Arai Y, Umeyama M, and Kurosu S are employees of EA Pharma Co., Ltd., Japan. Kuramoto K is an employee of Kissei Pharmaceutical Co., Ltd., Japan.

Data Availability Statement

Data analyzed in this study are available from the corresponding author upon reasonable request.

Author Contributions

Conceptualization: Suzuki Y. Data curation: Nagaki A, Arai Y, Umeyama M, Kurosu S, Kuramoto K. Formal analysis: all authors. Investigation: Saruta M, Omori T, Suzuki Y. Methodology: Suzuki Y. Project administration: Saruta M, Omori T, Suzuki Y. Supervision: Suzuki Y. Writing–original draft: Saruta M. Writing–review & editing: all authors. Approval of final manuscript: all authors.

Additional Contributions

The authors thank Helen Roberton of Edanz (www.edanz.com) for providing medical writing support in accordance with Good Publication Practice guidelines (http://www.ismpp.org/gpp-2022). The authors also thank A2 Healthcare Corporation, Japan, for data management and statistical analysis services, along with all investigators at the centers participating in this post-marketing surveillance.

Supplementary Material

Supplementary materials are available at the Intestinal Research website (https://www.irjournal.org).

SUPPLEMENTARY METHODS: PATIENT QUESTIONNAIRE

Percentage of Months Spent in PRO2-Symptomatic Remission within the First 24 Months and by Semester in Patients Included in Efficacy-Based or Acceptability-Based Strategies

ir-2025-00164-Supplementary-Methods.pdf

Supplementary Table 1.

Concomitant Use of Oral 5-ASA Preparations (Safety Analysis Population; n=633)

ir-2025-00164-Supplementary-Table-1.pdf

Supplementary Table 2.

Incidence of Adverse Drug Reactions by Background Factors (Safety Analysis Population)

ir-2025-00164-Supplementary-Table-2.pdf

Supplementary Table 3.

Patient Acceptance of Treatment by Self-Reported Questionnaire (Effectiveness Analysis Population)

ir-2025-00164-Supplementary-Table-3.pdf

Supplementary Fig. 1.

Kaplan–Meier estimation of cumulative clinical remission in partial Mayo score (effectiveness analysis population). CI, confidence interval.

ir-2025-00164-Supplementary-Fig-1.pdf

Supplementary Fig. 2.

Achievement of rectal bleeding score 0 (effectiveness analysis population).

ir-2025-00164-Supplementary-Fig-2.pdf

Supplementary Fig. 3.

Change in health condition visual analogue scale (effectiveness analysis population). Values are presented as mean±standard deviation, ****P<0.0001 vs. baseline (week 0) scores.

ir-2025-00164-Supplementary-Fig-3.pdf

Supplementary Fig. 4.

Time period when patients felt effects (effectiveness analysis population).

ir-2025-00164-Supplementary-Fig-4.pdf

Supplementary Fig. 5.

Change in endoscopy score. Values are presented as mean±standard deviation, ****P<0.0001 vs. baseline (week 0) scores.

ir-2025-00164-Supplementary-Fig-5.pdf

Fig. 1.

Patient disposition. ^aOff-label use was defined as prescribing to pediatric patients or daily doses other than 2 mg twice daily throughout the administration period.

Fig. 2.

Effectiveness by partial Mayo score and subscores (effectiveness analysis population). (A) Clinical remission rate in partial Mayo score (95% confidence intervals denoted in brackets). (B) Partial Mayo score. (C) Stool frequency. (D) Rectal bleeding. (E) Physician’s global assessment. Values are presented as mean±standard deviation, ****P<0.0001 vs. baseline (week 0) scores.

Fig. 3.

Partial Mayo score by background factors (effectiveness analysis population). (A) Disease phenotype, (B) severity, (C) clinical course, (D) age, (E) prior administration of topical therapy, (F) use of advanced therapy (biological agent or JAK inhibitors) at baseline. JAK, Janus kinase. Values are presented as mean±standard deviation, **P<0.01, ***P<0.001, ****P<0.0001 vs. baseline (week 0) scores. For panel D, *P> 0.05 for age (<65 years vs. ≥65 years).

Table 1.

Patient Demographics and Baseline Characteristics

Characteristic	Safety analysis population (n=633)
Sex
Male	340 (53.7)
Female^a	293 (46.3)
Age (yr)
Mean ± SD	45.6 ± 15.6
<15	3 (0.5)
15–64	542 (85.6)
≥65	88 (13.9)
Body mass index (kg/m²)
Mean ± SD	22.5 ± 3.7
<18.5	60 (9.5)
≥18.5 and <25.0	343 (54.2)
≥25.0	106 (16.7)
Patient setting
Outpatient	611 (96.5)
Inpatient	22 (3.5)
Duration of disease (yr)
<1	116 (18.3)
≥1 and <5	189 (29.9)
≥5 and <10	143 (22.6)
≥10 and <20	134 (21.2)
≥20	48 (7.6)
Unknown	3 (0.5)
Disease phenotype
Pancolitis	245 (38.7)
Left-sided colitis	250 (39.5)
Proctitis	138 (21.8)
Disease severity
Mild	196 (31.0)
Moderate	426 (67.3)
Unknown	11 (1.7)
Clinical course
First onset	94 (14.8)
Relapsing–remitting	433 (68.4)
Chronic continuous	106 (16.7)
Smoking
Current smoker	62 (9.8)
Complications
Yes	211 (33.3)
Impairment of hepatic function	10 (1.6)
Renal impairment	4 (0.6)
Medical history
Yes	111 (17.5)
Prior medications
Yes	588 (92.9)
Oral 5-ASA	554 (87.5)
JAK inhibitors	3 (0.5)
Immunomodulators	105 (16.6)
Oral corticosteroids	64 (10.1)
Biological agents	48 (7.6)
IV corticosteroids	8 (1.3)
5-ASA suppository	90 (14.2)
5-ASA enema	41 (6.5)
Topical steroid preparation	16 (2.5)
Active live bacteria preparation	241 (38.1)
Concomitant medications
Yes	612 (96.7)
Oral 5-ASA	579 (91.5)
JAK inhibitors	5 (0.8)
Immunomodulators	118 (18.6)
Oral corticosteroids	79 (12.5)
Biological agents	58 (9.2)
IV corticosteroids	6 (0.9)
5-ASA suppository	64 (10.1)
5-ASA enema	12 (1.9)
Topical steroid preparation	7 (1.1)
Active live bacteria preparation	246 (38.9)

Values are presented as number (%) unless otherwise indicated.

^a Among female patients (n=293), 2 were pregnant (0.7%).

SD, standard deviation; 5-ASA, 5-aminosalicylic acid; JAK, Janus kinase; IV, intravenous.

Table 2.

Details of Treatment with Budesonide 2-mg Rectal Foam

Treatment detail		Safety analysis population (n=633)
Treatment duration (day)	Mean ± SD	55.0 ± 25.5
	Median (IQR)	56.0 (38.0–85.0)
Duration of treatment (wk)	<2	29 (4.6)
	≥2 and <6	143 (22.6)
	≥6 and ≤12	281 (44.4)
	>12	180 (28.4)
Reason for treatment discontinuation^a	Improvement of disease condition	315 (69.5)
(multiple choices were possible)	Ineffective	69 (15.2)
	Failure to attend follow-up visits during the study	19 (4.2)
	Refusal of treatment	19 (4.2)
	Adverse events	11 (2.4)
	Others	24 (5.3)
Dose/frequency of dosing^b	Twice-daily dosing	504 (79.6)
	Other than twice-daily dosing	129 (20.4)

Values are presented as number (%) unless otherwise indicated.

^a The denominator is the number of cases in which dosing was completed within 12 weeks.

^b Twice-daily dosing denotes cases in which the drug was administered at a dose of 1 push (2 mg) twice daily throughout the treatment period, that is, the approved dosage regimen. Other than twice-daily dosing denotes cases in which the drug was administered outside the approved dosage regimen at least once during treatment with the drug.

SD, standard deviation; IQR, interquartile range.

Table 3.

Incidence of ADRs by MedDRA Preferred Term (Safety Analysis Population)

	No. (%) (n=633)
ADRs	27 (4.3)
Cystitis^a	1 (0.2)
Gastroenteritis^a	1 (0.2)
Gastroenteritis viral^a	1 (0.2)
Nasopharyngitis^a	1 (0.2)
Cytomegalovirus enterocolitis^b	1 (0.2)
Enteritis infectious^b	1 (0.2)
Insomnia^a	1 (0.2)
Headache	4 (0.6)
Migraine	1 (0.2)
Hypertension^a	1 (0.2)
Upper respiratory tract inflammation	2 (0.3)
Abdominal distention	1 (0.2)
Abdominal pain	1 (0.2)
Anal fissure	1 (0.2)
Constipation	1 (0.2)
Hematochezia	1 (0.2)
Nausea	1 (0.2)
Acne^a	1 (0.2)
Alopecia	1 (0.2)
Dermatitis contact	1 (0.2)
Hypertrichosis	1 (0.2)
Pruritus	1 (0.2)
Bursitis	1 (0.2)
Muscle spasms	1 (0.2)
Musculoskeletal stiffness	1 (0.2)
Genital hemorrhage	1 (0.2)
Edema^a	1 (0.2)
Pyrexia	1 (0.2)

^a Glucocorticoid-related ADRs. One patient experienced 2 glucocorticoidrelated ADRs.

^b Serious ADRs.

ADRs, adverse drug reactions; MedDRA, Medical Dictionary for Regulatory Activities Japanese version (24.0).

Table 4.

Multivariate Analysis of Factors Affecting Clinical Remission (Effectiveness Analysis Population)

Factor		Multivariate analysis
Factor		No.	Patients with remission^a, No. (%)	OR (95% CI)	P-value
Clinical course	First onset	65	54 (83.1)	Reference
	Relapsing–remitting	278	164 (59.0)	0.334 (0.165–0.677)	0.0023
	Chronic continuous	53	34 (64.2)	0.449 (0.183–1.101)	0.0803
Prior administration of topical therapy	No	316	213 (67.4)	Reference
	Yes	80	39 (48.8)	0.433 (0.257–0.728)	0.0016
Prior administration of advanced therapy^b	No	365	241 (66.0)	Reference
	Yes	31	11 (35.5)	0.298 (0.135–0.657)	0.0027
Partial Mayo score at start of treatment	0–3	42	34 (81.0)	2.749 (1.165–6.486)	0.0210
	3–6	201	127 (63.2)	Reference
	6–9	153	91 (59.5)	0.859 (0.546–1.351)	0.5104

^a Number of cases in remission at final evaluation. Cases with missing partial Mayo score data were considered as “no remission.”

^b Biological agent or Janus kinase inhibitor.

OR, odds ratio; CI, confidence interval.

REFERENCES

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3. Paoluzi OA, Iacopini F, Pica R, et al. Comparison of two different daily dosages (2.4 vs. 1.2 g) of oral mesalazine in maintenance of remission in ulcerative colitis patients: 1-year follow-up study. Aliment Pharmacol Ther 2005;21:1111–1119.Article PubMed
4. O’Donnell S, O’Morain CA. Therapeutic benefits of budesonide in gastroenterology. Ther Adv Chronic Dis 2010;1:177–186.Article PubMed PMC PDF
5. Sandborn WJ, Bosworth B, Zakko S, et al. Budesonide foam induces remission in patients with mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. Gastroenterology 2015;148:740–750.e2.Article PubMed
6. Naganuma M, Aoyama N, Tada T, et al. Complete mucosal healing of distal lesions induced by twice-daily budesonide 2-mg foam promoted clinical remission of mild-to-moderate ulcerative colitis with distal active inflammation: doubleblind, randomized study. J Gastroenterol 2018;53:494–506.Article PubMed PDF
7. Omori T, Saruta M, Nagaki A, et al. Real-world safety and efficacy of twice-daily budesonide 2-mg foam in patients with ulcerative colitis: interim analysis of post-marketing surveillance. Expert Opin Pharmacother 2021;22:1505–1511.Article PubMed
8. Pharmaceutical and Medical Devices Agency. Rectabul^® 2 mg rectal foam 14 doses [Internet]. c2025 [cited 2025 Feb 2]. https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/111890_2399716K1020_1_08.
9. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis: a randomized study. N Engl J Med 1987;317:1625–1629.Article PubMed
10. Naganuma M, Aoyama N, Suzuki Y, et al. Twice-daily budesonide 2-mg foam induces complete mucosal healing in patients with distal ulcerative colitis. J Crohns Colitis 2016;10:828–836.Article PubMed
11. Watanabe K, Hirai F, Kobayashi K, et al. Impact of twice-daily budesonide foam administration on early clinical response and endoscopic remission in patients with ulcerative colitis: a post hoc analysis. J Gastroenterol Hepatol 2024;39:2367–2376.Article PubMed PMC
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13. Gross V, Bar-Meir S, Lavy A, et al. Budesonide foam versus budesonide enema in active ulcerative proctitis and proctosigmoiditis. Aliment Pharmacol Ther 2006;23:303–312.Article PubMed
14. Kobayashi T, Moriya K, Fujii T, et al. Early resolution of bowel urgency by budesonide foam enema results in improved quality of life in patients with ulcerative colitis: a multicenter prospective observational study. Intest Res 2025;23:157–169.Article PubMed PDF
15. Miyazaki R, Sakurai T, Shimada M, et al. Bowel frequency (night) and urgent defecation are improved by budesonide foam in patients with ulcerative colitis: a retrospective observational study. BMC Gastroenterol 2022;22:310.Article PubMed PMC PDF
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Safety and effectiveness of budesonide rectal foam for ulcerative colitis in a large-scale, multicenter, prospective observational study: final report of post-marketing surveillance in Japan

DOI: https://doi.org/10.5217/ir.2025.00164

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Early resolution of bowel urgency by budesonide foam enema results in improved quality of life in patients with ulcerative colitis: a multicenter prospective observational study

Safety and effectiveness of budesonide rectal foam for ulcerative colitis in a large-scale, multicenter, prospective observational study: final report of post-marketing surveillance in Japan

Fig. 1. Patient disposition. aOff-label use was defined as prescribing to pediatric patients or daily doses other than 2 mg twice daily throughout the administration period.

Fig. 2. Effectiveness by partial Mayo score and subscores (effectiveness analysis population). (A) Clinical remission rate in partial Mayo score (95% confidence intervals denoted in brackets). (B) Partial Mayo score. (C) Stool frequency. (D) Rectal bleeding. (E) Physician’s global assessment. Values are presented as mean±standard deviation, ****P<0.0001 vs. baseline (week 0) scores.

Fig. 3. Partial Mayo score by background factors (effectiveness analysis population). (A) Disease phenotype, (B) severity, (C) clinical course, (D) age, (E) prior administration of topical therapy, (F) use of advanced therapy (biological agent or JAK inhibitors) at baseline. JAK, Janus kinase. Values are presented as mean±standard deviation, **P<0.01, ***P<0.001, ****P<0.0001 vs. baseline (week 0) scores. For panel D, *P> 0.05 for age (<65 years vs. ≥65 years).

Graphical abstract

Fig. 1.

Fig. 2.

Fig. 3.

Graphical abstract

Safety and effectiveness of budesonide rectal foam for ulcerative colitis in a large-scale, multicenter, prospective observational study: final report of post-marketing surveillance in Japan

Characteristic	Safety analysis population (n=633)
Sex
Male	340 (53.7)
Female^a	293 (46.3)
Age (yr)
Mean ± SD	45.6 ± 15.6
<15	3 (0.5)
15–64	542 (85.6)
≥65	88 (13.9)
Body mass index (kg/m²)
Mean ± SD	22.5 ± 3.7
<18.5	60 (9.5)
≥18.5 and <25.0	343 (54.2)
≥25.0	106 (16.7)
Patient setting
Outpatient	611 (96.5)
Inpatient	22 (3.5)
Duration of disease (yr)
<1	116 (18.3)
≥1 and <5	189 (29.9)
≥5 and <10	143 (22.6)
≥10 and <20	134 (21.2)
≥20	48 (7.6)
Unknown	3 (0.5)
Disease phenotype
Pancolitis	245 (38.7)
Left-sided colitis	250 (39.5)
Proctitis	138 (21.8)
Disease severity
Mild	196 (31.0)
Moderate	426 (67.3)
Unknown	11 (1.7)
Clinical course
First onset	94 (14.8)
Relapsing–remitting	433 (68.4)
Chronic continuous	106 (16.7)
Smoking
Current smoker	62 (9.8)
Complications
Yes	211 (33.3)
Impairment of hepatic function	10 (1.6)
Renal impairment	4 (0.6)
Medical history
Yes	111 (17.5)
Prior medications
Yes	588 (92.9)
Oral 5-ASA	554 (87.5)
JAK inhibitors	3 (0.5)
Immunomodulators	105 (16.6)
Oral corticosteroids	64 (10.1)
Biological agents	48 (7.6)
IV corticosteroids	8 (1.3)
5-ASA suppository	90 (14.2)
5-ASA enema	41 (6.5)
Topical steroid preparation	16 (2.5)
Active live bacteria preparation	241 (38.1)
Concomitant medications
Yes	612 (96.7)
Oral 5-ASA	579 (91.5)
JAK inhibitors	5 (0.8)
Immunomodulators	118 (18.6)
Oral corticosteroids	79 (12.5)
Biological agents	58 (9.2)
IV corticosteroids	6 (0.9)
5-ASA suppository	64 (10.1)
5-ASA enema	12 (1.9)
Topical steroid preparation	7 (1.1)
Active live bacteria preparation	246 (38.9)

Treatment detail		Safety analysis population (n=633)
Treatment duration (day)	Mean ± SD	55.0 ± 25.5
	Median (IQR)	56.0 (38.0–85.0)
Duration of treatment (wk)	<2	29 (4.6)
	≥2 and <6	143 (22.6)
	≥6 and ≤12	281 (44.4)
	>12	180 (28.4)
Reason for treatment discontinuation^a	Improvement of disease condition	315 (69.5)
(multiple choices were possible)	Ineffective	69 (15.2)
	Failure to attend follow-up visits during the study	19 (4.2)
	Refusal of treatment	19 (4.2)
	Adverse events	11 (2.4)
	Others	24 (5.3)
Dose/frequency of dosing^b	Twice-daily dosing	504 (79.6)
	Other than twice-daily dosing	129 (20.4)

	No. (%) (n=633)
ADRs	27 (4.3)
Cystitis^a	1 (0.2)
Gastroenteritis^a	1 (0.2)
Gastroenteritis viral^a	1 (0.2)
Nasopharyngitis^a	1 (0.2)
Cytomegalovirus enterocolitis^b	1 (0.2)
Enteritis infectious^b	1 (0.2)
Insomnia^a	1 (0.2)
Headache	4 (0.6)
Migraine	1 (0.2)
Hypertension^a	1 (0.2)
Upper respiratory tract inflammation	2 (0.3)
Abdominal distention	1 (0.2)
Abdominal pain	1 (0.2)
Anal fissure	1 (0.2)
Constipation	1 (0.2)
Hematochezia	1 (0.2)
Nausea	1 (0.2)
Acne^a	1 (0.2)
Alopecia	1 (0.2)
Dermatitis contact	1 (0.2)
Hypertrichosis	1 (0.2)
Pruritus	1 (0.2)
Bursitis	1 (0.2)
Muscle spasms	1 (0.2)
Musculoskeletal stiffness	1 (0.2)
Genital hemorrhage	1 (0.2)
Edema^a	1 (0.2)
Pyrexia	1 (0.2)

Factor		Multivariate analysis
Factor		No.	Patients with remission^a, No. (%)	OR (95% CI)	P-value
Clinical course	First onset	65	54 (83.1)	Reference
	Relapsing–remitting	278	164 (59.0)	0.334 (0.165–0.677)	0.0023
	Chronic continuous	53	34 (64.2)	0.449 (0.183–1.101)	0.0803
Prior administration of topical therapy	No	316	213 (67.4)	Reference
	Yes	80	39 (48.8)	0.433 (0.257–0.728)	0.0016
Prior administration of advanced therapy^b	No	365	241 (66.0)	Reference
	Yes	31	11 (35.5)	0.298 (0.135–0.657)	0.0027
Partial Mayo score at start of treatment	0–3	42	34 (81.0)	2.749 (1.165–6.486)	0.0210
	3–6	201	127 (63.2)	Reference
	6–9	153	91 (59.5)	0.859 (0.546–1.351)	0.5104

Table 1. Patient Demographics and Baseline Characteristics

Values are presented as number (%) unless otherwise indicated.

Among female patients (n=293), 2 were pregnant (0.7%).

SD, standard deviation; 5-ASA, 5-aminosalicylic acid; JAK, Janus kinase; IV, intravenous.

Table 2. Details of Treatment with Budesonide 2-mg Rectal Foam

Values are presented as number (%) unless otherwise indicated.

The denominator is the number of cases in which dosing was completed within 12 weeks.

Twice-daily dosing denotes cases in which the drug was administered at a dose of 1 push (2 mg) twice daily throughout the treatment period, that is, the approved dosage regimen. Other than twice-daily dosing denotes cases in which the drug was administered outside the approved dosage regimen at least once during treatment with the drug.

SD, standard deviation; IQR, interquartile range.

Table 3. Incidence of ADRs by MedDRA Preferred Term (Safety Analysis Population)

Glucocorticoid-related ADRs. One patient experienced 2 glucocorticoidrelated ADRs.

Serious ADRs.

ADRs, adverse drug reactions; MedDRA, Medical Dictionary for Regulatory Activities Japanese version (24.0).

Table 4. Multivariate Analysis of Factors Affecting Clinical Remission (Effectiveness Analysis Population)

Number of cases in remission at final evaluation. Cases with missing partial Mayo score data were considered as “no remission.”